Gene Tied to Osteoarthritis Progression

The IL-1Ra gene may help predict when knee OA will worsen.

09/24/2010 | By Jennifer Davis

Scientists say they have turned up a genetic clue that may help predict which people with knee osteoarthritis, or OA, are likely to see their disease progress.

The study, presented in 2010 at the World Congress on Osteoarthritis in Brussels, Belgium, involved data from the Johnston County Osteoarthritis Project, in North Carolina, which monitored 1,154 participants for up to 11 years to see when they got OA and how quickly it advanced.

Genetic tests were done on participants at the start of the study. In analysing those tests, researchers found nine genes associated with OA progression. The strongest association of the bunch involved a specific pattern of genetic variations in the interleukin-1 receptor antagonist, or IL-1Ra, gene.

These genetic factors nearly doubled the likelihood that a person’s OA would progress to a severe stage. Interleukin-1, or IL-1, is a chemical signal associated with inflammation and cartilage degradation.

“These genetic polymorphisms, which were previously found to be associated cross-sectionally with more severe knee OA, have now been shown to be associated with the development and progression or worsening of knee OA over time,” explains lead author Joanne M. Jordan, MD, director of the University of North Carolina’s Thurston Arthritis Research Center.

While researchers were able to see an association between these specific genetic variations and disease progression, they can’t explain why that is.

“It may have to do with the way molecules line up or fold or fit in their receptors, any of which can cause enzymes to behave differently from how they otherwise might,” Dr. Jordan says.

Dr. Jordan says more research is needed but she has hopes for what this discovery will mean down the road.

“This might make it possible to identify high-risk people in advance of getting OA or before it progresses,” she explains.

Scientists say they have turned up a genetic clue that may help predict which people with knee osteoarthritis, or OA, are likely to see their disease progress.

The study, presented in 2010 at the World Congress on Osteoarthritis in Brussels, Belgium, involved data from the Johnston County Osteoarthritis Project, in North Carolina, which monitored 1,154 participants for up to 11 years to see when they got OA and how quickly it advanced.

Genetic tests were done on participants at the start of the study. In analysing those tests, researchers found nine genes associated with OA progression. The strongest association of the bunch involved a specific pattern of genetic variations in the interleukin-1 receptor antagonist, or IL-1Ra, gene.

These genetic factors nearly doubled the likelihood that a person’s OA would progress to a severe stage. Interleukin-1, or IL-1, is a chemical signal associated with inflammation and cartilage degradation.

“These genetic polymorphisms, which were previously found to be associated cross-sectionally with more severe knee OA, have now been shown to be associated with the development and progression or worsening of knee OA over time,” explains lead author Joanne M. Jordan, MD, director of the University of North Carolina’s Thurston Arthritis Research Center.

While researchers were able to see an association between these specific genetic variations and disease progression, they can’t explain why that is.

“It may have to do with the way molecules line up or fold or fit in their receptors, any of which can cause enzymes to behave differently from how they otherwise might,” Dr. Jordan says.

Dr. Jordan says more research is needed but she has hopes for what this discovery will mean down the road.

“This might make it possible to identify high-risk people in advance of getting OA or before it progresses,” she explains.

Identifying high-risk patients for inclusion in a clinical trial or for early intervention or even preventive efforts would be a big deal. Despite the pervasiveness of OA, researchers say it’s been difficult to develop drugs to treat the condition in part because they don’t know whose disease will progress and whose won’t. There are currently no drugs to treat or stop the progression of the disease.

Dr. Jordan says her team still needs to analyze data from the African-American participants in the study, and she says overall there is still much to learn.

“It is important to recognize that OA is likely related to many genes, and we are particularly interested in how genes interact with other genes and with various risk factors in the environment,” Dr. Jordan says.

Eric Matteson, MD, a professor of Rheumatology at the Mayo Clinic in Rochester, Minn., says the findings of this study make sense given what’s known about the inflammatory protein.

“Its something that I think is important. It’s pretty novel because what it shows is not only in the test tube – but maybe in real people – an abnormality like this plays a role in causing OA,” Dr. Matteson says. “We’re not at the point where we can say we’re going to test for the gene. But it’s a further piece that advances understanding of how OA occurs.”

Dr. Matteson says sometimes associations of gene products don’t hold up over time because things can be discovered by chance. But he thinks the strength of this association is good and he thinks the study offers intriguing possibilities for the future.

“We have drugs that antagonize the effects of interleukin-1, so you wonder if there might be some treatment consequences. And it may be that in certain settings you might even test for the gene and then can you alter that gene? Those are questions way down the road but they are interesting things to think about with this.”